A number of peptide growth factors involved in a broad range of cellular processes including hyperplasia, DNA synthesis, differentiation, cell cycle progression, and inhibition of apoptosis are known, and include the insulin-like growth factors (IGFs, e.g., IGF-I and IGF-II) (Jones & Clemmons, 1995, Endocrine Rev. 16 3; Wood & Yee, 2000, J. Mammary Gland Biology and Neoplasia 5 1), EGF (Heldin et al., 1981, Science 4 1122), bFGF (Taraboletti et al., 1997, Cell Growth. Differ. 8 471), and KGF (Marchese et al., 1990, J. Cell Physiol. 144 326). These effects are mediated through binding to their cognate tyrosine-kinase linked cell surface receptors, the type 1 IGF receptor (IGF-IR), EGF receptor, bFGF receptor, and KGF receptor, respectively. The IGFs are also tightly regulated by a family of specific binding proteins, termed IGFBPs, whose primary role is to bind free IGFs and thereby moderate their half-life, specificity and activity (Clemmons, 1998, Mol. Cell. Endoerinol. 140 19).
Fibronectin is a high molecular mass adhesive glycoprotein found in all vertebrates. Fibronectin plays a role in cell adhesion, cell morphology and surface architecture. It's main function seems to be its involvement in cellular migration during development, tissue repair and wound healing, regulation of cell growth, and differentiation (Alitalo & Vaheri, 1982, Adv. Cancer Res. 37 111; Yamada, 1983, Annu. Rev. Biochem. 62 761; Hynes, 1985, Annu. Rev. Cell Biol. 1 67). Fibronectin polymorphism is due to alternative splicing patterns in three regions (ED-A, ED-B and IIICS) of the single fibronectin primary transcript (Petersen et al., 1983, Proc. Natl. Acad. Sci. USA 80 137; Schwarzbauer et al., 1983, Cell 35 421; Kornblihtt et al., 1984, Nucleic Acids Res. 12 5853). The exact composition of fibronectin depends on the tissue type and/or cellular conditions. In humans, there are potentially 20 different forms of fibronectin, most arising from alternative splicing of some type 3 modules (Potts and Campbell, 1994, Curr. Opin. Cell Biol. 6 648). Expression of fibronectin splicing variants appears to be both developmentally regulated and tissue-specific.
Fibronectin has the ability to bind a number of extracellular molecules, including heparin, collagen and hyaluronic acid. Fibronectin organizes cell-cell interactions and cellular interaction with the extracellular matrix by binding to different components of the extracellular matrix and to membrane-bound fibronectin receptors (integrins) on cell surfaces.
However, the relative contributions of growth factors and fibronectin, and their respective domains, present in protein complexes, in terms of stimulating biological responses such as cell migration and/or proliferation, have remained elusive.